Elevated serum total homocysteine (tHcy) is an independent risk factor for vascular diseases. Associations between serum tHcy and demographics, health and lifestyle factors, and blood vitamin concentrations were investigated. Data from the third National Health and Nutrition Examination Survey, 1988-1994 were used to examine associations in men (n = 2965) and women (n = 3580) between tHcy and age, sex, race-ethnicity, body mass index, systolic and diastolic blood pressures, alcohol consumption, supplement use, red blood cell (RBC) folate, and serum creatinine, folate, vitamin B-12, and cotinine (a measure of cigarette smoking). The unadjusted mean tHcy was 21.5% ( approximately 1.9 micro mol/L) higher in men than in women, 11.8% ( approximately 1.1 micro mol/L) higher in non-Hispanic whites than in Mexican Americans, 42% ( approximately 3.7 micro mol/L) higher in persons aged > or = 70 y than in persons aged < 30 y, and 10.9% ( approximately 1.0 micro mol/L) higher in supplement nonusers than in supplement users. The tHcy concentration was negatively associated with serum folate (P < 0.0001 for trend), RBC folate (P < 0.0001 for trend), and serum vitamin B-12 (P < 0.0036 for trend) and was positively associated with alcohol consumption (P < 0.0001 for trend), serum cotinine (P < 0.0001 for trend), and systolic blood pressure (P < 0.0001 for trend). Consumption of hard liquor (but not of beer or wine) was positively associated with tHcy concentration (P < 0.0001 for trend). In this population-based study, the significant predictors of tHcy concentration were sex, age, race-ethnicity, serum creatinine, systolic blood pressure, body mass index, hard-liquor consumption, smoking, supplement use, serum folate, RBC folate, and serum vitamin B-12.